Project Summary/Abstract The Epigenetics and Regulation Program cultivates research collaborations between its members as well as with researchers from other USC Norris Research Programs and peer institutions. These efforts have resulted in: 1) breakthroughs in understanding the basic mechanisms that regulate growth and behavior of normal and cancer cells; and 2) translation of USC Norris findings into new methods for cancer prevention, detection, prognosis, and treatment. The Program integrates research in genomics and epigenetics, cell signaling, and normal and cancer stem cells in order to achieve the overarching goal of understanding regulation in cancer. Members jointly develop and employ novel genomic and epigenomic technologies and computational approaches in order to analyze genes and their regulation and genetic variation in cancers, at the mechanistic level and in large-scale comparative studies. They also study selected critical signaling pathways that drive cancer development and progression with the ultimate goals of understanding cancer risk loci, developing new diagnostic tools, identifying new therapeutic targets, and translating discoveries through collaborations with clinical researchers. Member interactions are fostered through retreats and weekly meetings focused on regulation, epigenetics, bioinformatics, and stem cells that have resulted in a number of inter- and intra- programmatic collaborations. The Program fosters member interactions and drives novel collaborations through its leadership in cancer-focused PhD training programs and by including predoctoral and postdoctoral trainees in weekly Program meetings. Drs. Michael Stallcup and Peggy Farnham co-lead the Program. Dr. Stallcup is an expert in steroid hormone signaling and the regulation of chromatin and transcription by transcription factors and their coregulators, while Dr. Farnham is a leader in genomics, epigenetics, and genome-wide methods of analysis. The Program has 26 members from 18 departments and five schools. Program members have $10M in peer-reviewed funding (direct costs), of which 14% is from NCI, 50% is from NIH, and 30% from other peer-review funding sources. During the project period, members had 445 cancer- relevant publications, of which 31% were inter-programmatic, 23% were intra-programmatic, and 32% were inter-institutional.